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BreastTrue® Targeted Panels

A Genetic Testing for Breast Cancer

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what is brcatrue® Ashkenazi Jewish (3-Site)?

BRCATrue® – Ashkenazi Jewish (3-site) is a site-specific genetic testing panel consisting of the three common BRCA1 and BRCA2 pathogenic variants found in the Ashkenazi Jewish population. These three mutations are defined as BRCA1 c.68_69delAG (also known as c.185delAG and c.187delAG), BRCA1 c.5266dupC (also known as c.5382insC), and BRCA2 c.5946delT (c.6174delT). Overall, these three pathogenic variants account for approximately 90-95% of all BRCA1 and BRCA2 pathogenic variants in individuals of Ashkenazi Jewish descent.1-2

what is brcatrue®
HISPANIC (8-Site)?

BRCATrue® – Hispanic (8-Site) is a site-specific genetic testing panel consisting of eight recurrent BRCA1 and BRCA2 pathogenic variants found in the Mexican population (see table below). Overall, these eight pathogenic variants account for approximately 36-65% of all BRCA1 and BRCA2 mutations in individuals of Mexican descent.3-4

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Step 1:

BreastTrue® Targeted Panels must be ordered by a physician, and patients are required to fill out a clinical history questionnaire to determine eligibility.
Physicians can request test kits here.

Step 2:

Patient’s saliva or blood sample is collected in the BreastTrue® Targeted Panels test kit and sent back to Pathway Genomics, along with the required paperwork.

Step 3:

Pathway Genomics analyzes your sample in its CLIA-certified and CAP-accredited laboratory. Typically within two to three weeks, your personalized results will be available to the ordering health care professional. The results will then be released to you. Pathway Genomics has a team of genetic counselors who are available to ensure that you understand the information in your report, and to answer any questions you may have about your results . To contact our genetic counselors, please call our client services department at 877-505-7374 or email clientservices@pathway.com.

BRCATrue® - Ashkenazi Jewish (3-site)

Test Description

It is important to note that this is a targeted panel and does not account for all pathogenic variants in BRCA1 and BRCA2 within the Ashkenazi Jewish population. Follow-up comprehensive BRCA1 and BRCA2 testing should be considered in the event of a negative result, as well as a cancer history suggestive of Hereditary Breast and Ovarian Cancer syndrome. Pathway Genomics offers two easy-to-use reflexive options in combination with the BRCATrue® – Ashkenazi Jewish test. These options allow the provider to automatically reflex to a more comprehensive test (BRCATrue® or BreastTrue® High Risk Panel) in the event that a pathogenic variant is not found on the initial BRCATrue® – Ashkenazi Jewish test.

Test Resources

  1. Test Requisition Form
  2. Sample Report

Appropriate Candidates for Testing

BRCATrue® – Ashkenazi Jewish (3-site) should be considered for individuals of Ashkenazi Jewish descent with a personal and/or family history of the following risk factors:

  • Early onset breast cancer (diagnosed when less than 50 years old)
  • Breast and ovarian cancer in the same individual
  • Bilateral or multiple breast cancers in the same individual
  • Triple-negative breast cancer
  • Multiple relatives on the same side of the family with the same (or related) cancers
  • Male breast cancer and/or other rare associated cancers

BRCATrue® - Hispanic (8-site)

Test Description

It is important to note that this is a targeted panel, and does not account for all possible pathogenic variants in BRCA1 and BRCA2 within the Hispanic or Mexican population. Follow-up comprehensive BRCA1 and BRCA2 testing is recommended in the event of a negative result, as well as a cancer history suggestive of Hereditary Breast and Ovarian Cancer syndrome. Pathway Genomics offers two easy-to-use reflexive options in combination with the BRCATrue® – Hispanic (8-Site) test. These options allow the provider to automatically reflex to a more comprehensive test (BRCATrue® or BreastTrue® High Risk Panel) in the event that a pathogenic variant is not found on the initial BRCATrue® – Hispanic (8-Site) test.

Additionally, for individuals that have previously had comprehensive BRCA1 and BRCA2 testing (full sequencing with deletion/duplication analysis), the BRCATrue® – Hispanic (8-Site) test is not recommended nor clinically indicated.


BRCATrueHispanic-GeneMutation-Chart


Test Resources

  1. Test Requisition Form
  2. Testing Summary
  3. One-pager
  4. White Paper
  5. Sample Report

Appropriate candidates for testing:

BRCATrue® – Hispanic (8-Site) should be considered for individuals of Mexican descent with a personal and/or family history of the following risk factors:

  • Early onset breast cancer (diagnosed when less than 50 years old)
  • Breast and ovarian cancer in the same individual
  • Bilateral or multiple breast cancers in the same individual
  • Triple-negative breast cancer
  • Multiple relatives on the same side of the family with the same (or related) cancers
  • Male breast cancer and/or other rare associated cancers

BRCA1/2 and Hereditary Cancer

BRCA1 description

Pathogenic variants in the BRCA1 gene are associated with Hereditary Breast and Ovarian Cancer syndrome. They convey a significantly increased risk of both breast and ovarian cancer. Studies have demonstrated that pathogenic variants in BRCA1 can be associated with up to a 85% breast cancer risks and up to a 63% ovarian cancer risk. Furthermore, women with a pathogenic variant in BRCA1 pathogenic variant have an increased risk of a recurrent breast cancer diagnosis (contralateral or ipsilateral). This risk has estimated to be up to 27% within the first 5 years of initial diagnosis and up to 40-50% within 20 years of initial diagnosis. Pathogenic variants in BRCA1 may also be associated with an increased risk of other types of cancer, including peritoneal, pancreatic, prostate, and male breast cancer. 5-12

BRCA2 description

Pathogenic variants in the BRCA2 gene are associated with Hereditary Breast and Ovarian Cancer (HBOC) syndrome. They convey a significantly increased risk of several cancers including breast, ovarian, pancreatic, melanoma, and prostate cancer. Studies have demonstrated that pathogenic variants in BRCA2 can be associated with up to an 84% breast cancer risk and up to a 27% ovarian cancer risk. Furthermore, women with a pathogenic variant in BRCA2 have an increased risk of a recurrent breast cancer diagnosis (contralateral or ipsilateral). This risk is estimated to be up to 12% within the first 5 years of initial diagnosis and up to 40–50% within 20 years of initial diagnosis. BRCA2 pathogenic variants may also be associated with small increased risks of developing primary peritoneal, gallbladder, bile duct, and stomach cancer. However, these risks are not yet clearly defined. 5-14



Inheritance and Familial Implications

BRCA1 and BRCA2 pathogenic variants are found in both men and women, though the cancer risks vary between the two genders. These variants are passed through families in an autosomal dominant pattern, meaning that an individual with a pathogenic variant has a 50% chance of passing it on to each of his or her children. Conversely, this also means that there is a 50% chance of not passing on the pathogenic variant to each child. In addition, each first-degree relative (parents, full siblings, and children) of someone with a pathogenic variant in BRCA1 and BRCA2 have a 50% chance of having the same variant.

Genetic testing is available to at-risk family members to determine if they also carry the identified BRCA1 or BRCA2 pathogenic variant. Identified carriers of a pathogenic variant in BRCA1 or BRCA2 should seek recommendations from their provider regarding future medical management due to the increased risk for certain cancers. Individuals found not to carry the familial pathogenic variant in BRCA1 or BRCA2 gene will have cancer risks similar to that of the general population.

Testing Options

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*Ashkenazi Jewish (AJ) Founder mutations include: BRCA1: 185delAG and 5382insC, and BRCA2: 6174delT

**The recurrent BRCA1 and BRCA2 pathogenic variants found on the BRCATrue-Hispanic test include: BRCA1 c.68_69delAG , c.212+1G>A, exon9-12del, c.2433delC (2552delC), c.2864C>A (p.S955X), c.4327C>T (p.1443X), c.5266dupC (5382insC) and BRCA2 c.3264dupT (3492insT).

BlueArrowDenotes that there is an option to reflex to comprehensive BRCA1 and BRCA2 analysis, including full sequencing and deletion/duplication analysis.

GreenArrowDenotes that there is an option to reflex to the BreastTrue® High Risk Panel. This testing will include full sequencing and deletion/duplication analysis of the following genes: BRCA1 and BRCA2 (if not already completed), as well as CDH1, PALB2, PTEN, STK11, and TP53.

References

References

  1. Kauff ND, Perez-Segura P, Robson ME et al. (2002). Incidence of non-founder BRCA1 and BRCA2 mutations in high risk Ashkenazi breast and ovarian cancer families. J Med Genet 39(8), 611-614.
  2. Frank TS, Deffenbaugh AM, Reid JE et al. (2002). Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol. 20(6):1480-90.
  3. Villarreal-Garza, C., Alvarez-Gomez, R. M., Perez-Plasencia, C. et al. (2014) Significant clinical impact of recurrent BRCA1 and BRCA2 mutations in Mexico. Cancer 121(3), 372-8.
  4. Weitzel, J. N., Clague, J., Martir-Negron, et al. (2013) Prevalence and type of BRCA mutations in Hispanics undergoing genetic cancer risk assessment in the southwestern United States: a report from the Clinical Cancer Genetics Community Research Network. Journal of clinical oncology. Official Journal of the American Society of Clinical Oncology 31, 210-216.
  5. Daly M, et al. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast and Ovarian. V2.2014. Accessed 01/2015. Available at http://www.nccn.org.
  6. Petrucelli N, Daly MB, Feldman GL. BRCA1 and BRCA2 Hereditary Breast and Ovarian Cancer. 1998 Sep 4 [Updated 2013 Sep 26]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1247/.
  7. Chen and Parmigiani. (2007). Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 25(11), 1329-33, PMID 17416853.
  8. Van det Kolk et at. (2010). Penetrance of breast cancer, ovarian cancer and contralateral breast cancer in BRCA1 and BRCA2 families: high cancer incidence at older age. Breast Cancer Res Treat. 124(3), 643-51, PMID 20204502.
  9. Metcalfe et al. (2004). Contralateral breast cancer in BRCA1 and BRCA2 pathogenic variant carriers. J Clin Oncol. 22(12), 2328-35, PMID 15197194.
  10. Finch et al. (2006). Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Pathogenic variant. JAMA 296(2), 185-92, PMID 16835424.
  11. Tai et al. (2007). Breast cancer risk among male BRCA1 and BRCA2 pathogenic variant carriers. J Natl Cancer Inst. 99(23), 1811-4, PMID 18042939.
  12. Risch et al. (2001). Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet. 68(3), 700-10, PMID 11179017.
  13. Breast Cancer Linkage Consortium. (1999). Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst. 91(15), 1310-6, PMID 10433620.
  14. van Asperen et al. (2005) Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet. 42(9), 711-9, PMID 16141007